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Query: UMLS:C0018799 (
heart disease
)
34,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital
heart disease
(C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital
heart disease
(A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo, we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of
VEGFA
and VEGFR
2
, and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo "naturally hypoxic precondition" present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients.
...
PMID:Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering. 3176 87
Endothelial cells (ECs) form the lining of lymph and blood vessels. Changes in tissue requirements or wounds may cause ECs to behave as tip or stalk cells. Alternatively, they may differentiate into mesenchymal cells (MCs). These processes are known as EC activation and endothelial-to-mesenchymal transition (EndMT), respectively. EndMT, Tip, and Stalk EC behaviors all require SNAI1, SNAI2, and Matrix metallopeptidase (MMP) function. However, only EndMT inhibits the expression of VE-cadherin, PECAM1, and VEGFR2, and also leads to EC detachment. Physiologically, EndMT is involved in heart valve development, while a defective EndMT regulation is involved in the physiopathology of cardiovascular malformations, congenital
heart disease
, systemic and organ fibrosis, pulmonary arterial hypertension, and atherosclerosis. Therefore, the control of EndMT has many promising potential applications in regenerative medicine. Despite the fact that many molecular components involved in EC activation and EndMT have been characterized, the system-level molecular mechanisms involved in this process have not been elucidated. Toward this end, hereby we present Boolean network model of the molecular involved in the regulation of EC activation and EndMT. The simulated dynamic behavior of our model reaches fixed and cyclic patterns of activation that correspond to the expected EC and MC cell types and behaviors, recovering most of the specific effects of simple gain and loss-of-function mutations as well as the conditions associated with the progression of several diseases. Therefore, our model constitutes a theoretical framework that can be used to generate hypotheses and guide experimental inquiry to comprehend the regulatory mechanisms behind EndMT. Our main findings include that both the extracellular microevironment and the pattern of molecular activity within the cell regulate EndMT. EndMT requires a lack of
VEGFA
and sufficient oxygen in the extracellular microenvironment as well as no FLI1 and GATA2 activity within the cell. Additionally Tip cells cannot undergo EndMT directly. Furthermore, the specific conditions that are sufficient to trigger EndMT depend on the specific pattern of molecular activation within the cell.
...
PMID:A Computational Model of the Endothelial to Mesenchymal Transition. 3222 39
The
vascular endothelial growth factor
(
VEGF
), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis. Angiogenesis, the formation of new blood vessels, is responsible for a wide variety of physio/pathological processes, including cardiovascular diseases (CVD). Cardiomyocytes (CM), the main cell type present in the heart, are the source and target of
VEGF-A
and express its receptors, VEGFR1 and VEGFR2, on their cell surface. The relationship between
VEGF-A
and the heart is double-sided. On the one hand,
VEGF-A
activates CM, inducing morphogenesis, contractility and wound healing. On the other hand,
VEGF-A
is produced by CM during inflammation, mechanical stress and cytokine stimulation. Moreover, high concentrations of
VEGF-A
have been found in patients affected by different CVD, and are often correlated with an unfavorable prognosis and disease severity. In this review, we summarized the current knowledge about the expression and effects of
VEGF-A
on CM and the role of
VEGF-A
in CVD, which are the most important cause of disability and premature death worldwide. Based on clinical studies on angiogenesis therapy conducted to date, it is possible to think that the control of angiogenesis and
VEGF-A
can lead to better quality and span of life of patients with
heart disease
.
...
PMID:VEGF-A in Cardiomyocytes and Heart Diseases. 3272 51
Pulmonary hypertension due to left
heart disease
(PH-LHD; Group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most frequent cause of PH. Despite its prevalence, no effective therapies for PH-LHD are available at present. This is largely due to the lack of a concise definition for hemodynamic phenotyping, existence of significant gaps in the understanding of the underlying pathology and the impact of associated comorbidities, as well as the absence of specific biomarkers that can aid in the early diagnosis and management of this challenging syndrome. Currently, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are guideline-recommended biomarkers for the diagnosis and prognosis of heart failure (HF) and PH. Endothelin-1 (ET-1),
vascular endothelial growth factor
-D (VEGF-D), and microRNA-206 have also been recently identified as new potential circulating biomarkers for patients with PH-LHD. In this review, we aim to present the current state of knowledge of circulating biomarkers that can be used to guide future research toward diagnosis, refine specific patient phenotype, and develop therapeutic approaches for PH-LHD, with a particular focus on PH-HFpEF. Potential circulating biomarkers identified in pre-clinical models of PH-LHD are also summarized here.
...
PMID:Current Understanding of Circulating Biomarkers in Pulmonary Hypertension Due to Left Heart Disease. 3311 32
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